Cardiovascular Drugs and Therapy

, Volume 5, Issue 4, pp 753–761 | Cite as

Effect of palmitic acid and fatty acid binding protein on ventricular fibrillation threshold in the perfused rat heart

  • Mitsuyuki Makiguchi
  • Hideaki Kawaguchi
  • Mamoru Tamura
  • Hisakazu Yasuda
Experimental Pharmacology


The effects of increased free fatty acid (FFA) levels on ventricular arrhythmias remain controversial. Using ventricular fibrillation threshold (VFT), we examined the relationship between FFA levels and ventricular arrhythmias. Isolated rat hearts were perfused with palmitate bound to either albumin or fatty acid binding protein (FABP) by Langendorf’s method. The VFT was determined by electrical stimulation. Perfusion with 0.12 mM albumin alone, 0.12 mM palmitate bound to 0.12 mM albumin, and 0.36 mM palmitate bound to 0.12 mM albumin did not lower the VFT significantly. However, 0.60 mM palmitate bound to 0.12 mM albumin lowered VFT from 2.19 ± 0.20 mA to 1.56 ± 0.13 mA. The perfusion of 0.36 mM palmitate bound to 0.12 mM FABP lowered the VFT from 2.05 ± to 0.19 mA to 1.47 ± 0.23 mA, but 0.12 mM FABP alone did not affect the VFT. Perfusion with 0.36 mM palmitate bound to 0.12 mM FABP caused the VFT to fall more than perfusion with 0.36 mM palmitate bound to 0.12 mM albumin. Then the effects of verapamil perfusion or a low concentration of perfusate Ca2+ on VFT were examined. VFT was determined by electrical stimulation. Palmitate (0.6 mM) bound to 0.12 mM albumin lowered VFT. Verapamil 10−7 perfusion and a low concentration of Ca2+ (Ca2+ 1.67 mM) suppressed the FFA-induced fall of VFT. These results suggested that the arrhythmogenic action of FFA was related to Ca2+ overload in myocardial cells.

Key Words

free fatty acid fatty acid binding protein ventricular fibrillation threshold calcium overload 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kurien VA, Oliver MF. Serum free fatty acids after acute myocardial infarction and cerebral vascular occlusion.Lancet 1966;2:122–127.PubMedCrossRefGoogle Scholar
  2. 2.
    Ito K, Kawaguchi H, Tamura M, Yasuda H. Prostaglandin synthesis and free fatty acid release from hypoxic rat heart.Prog Lipid Res 1986;25:147–151.CrossRefGoogle Scholar
  3. 3.
    Kawaguchi H, Yasuda H. Prostacyclin biosynthesis and phospholipase activity in hypoxic rat myocardium.Circ Res 1988;62:1175–1181.PubMedGoogle Scholar
  4. 4.
    Oliver MF, Kurien VA, Greenwood TW. Relation between serum-free-fatty-acids and arrhythmias and death after acute myocardial infarction.Lancet 1968;l:710–715.CrossRefGoogle Scholar
  5. 5.
    Murnaghan MF. Effect of fatty acids on the ventricular arrhythmia threshold in the isolated heart of the rabbit.Br J Pharmacol 1981;73:909–915.PubMedGoogle Scholar
  6. 6.
    Opie LH. Effect of fatty acids on contractility and rhythm of the heart.Nature 1970;227:1055–1056.PubMedCrossRefGoogle Scholar
  7. 7.
    Opie LH, Norris RM, Thomas M, et al. Failure of high concentrations of circulating free fatty acids to provoke arrhythmias in experimental myocardial infarction.Lancet 1971;1:818–822.PubMedCrossRefGoogle Scholar
  8. 8.
    Wenzel DG, Kleoppel JW. Arrhythmogenicity of long-chain fatty acids for cultured rat heart myocytes.Toxicology 1976;15:105–112.CrossRefGoogle Scholar
  9. 9.
    Willebrands AF, Ter Welle HF, Tasseron SJA. The effect of a high molar FFA/albumin ratios in the perfused medium on rhythm and contractility of the isolated rat heart.J Mol Cell Cardiol 1973;5:259–273.CrossRefGoogle Scholar
  10. 10.
    Stremmel W, Strohmeyer G, Borchard F, et al. Isolation and partial characterization of fatty acid binding protein in rat liver plasma membranes.Proc Natl Acad Sci USA 1985;82:4–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Stremmel W. Uptake of fatty acid by jejunal mucosal cells is mediated by fatty acid binding protein.J Clin Invest 1988;82:2001–2010.PubMedCrossRefGoogle Scholar
  12. 12.
    Knowlton AA, Apstein CS, Saouf R, Brecher P. Leakage of heart fatty acid binding protein with ischemia and reperfusion in the rat.J Mol Cell Cardiol 1989;21:577–583.PubMedCrossRefGoogle Scholar
  13. 13.
    Araki R, Tamura M, Yamazaki I. The effect of intracellular oxygen concentration on lactate release, pyridine nucleotide reduction, and respiration rate in the rat cardiac tissue.Circ Res 1983;53:448–455.PubMedGoogle Scholar
  14. 14.
    Van Tyn RA, MacLean LD. Ventricular fibrillation threshold.Am J Physiol 1961;201:457–461.Google Scholar
  15. 15.
    Fujii S, Kawaguchi H, Yasuda H. Fatty acid binding protein in kidney of normotensive and genetically hypertensive rats.Hypertension 1987;10:93–99.PubMedGoogle Scholar
  16. 16.
    Fujii H, Kawaguchi H, Okamoto H, et al. Fatty acid binding protein of cardiac muscle in spontaneously hypertensive rats: Effect of hypertrophy and its regresson.J Mol Cell Cardiol 1988;20:229–787.CrossRefGoogle Scholar
  17. 17.
    Lam KT, Borkan S, Claffey KP, et al. Properties and differential regulation of two fatty acid binding protein in the kidney.J Biol Chem 1988;263:15762–15768.PubMedGoogle Scholar
  18. 18.
    Makiguchi M, Kawaguchi H, Yasuda H, Tamura M. The effect of intracellular oxygen concentration on the ventricular fibrillation in perfused rat heart.Adv Exper Med Biol 1987;215:305–308.Google Scholar
  19. 19.
    Henderson AH, Craig RJ, Gorlin R, Sonnenblick EH. Free fatty acids and myocardial function in perfused rat hearts.Cardiovasc Res 1970;4:466–472.PubMedCrossRefGoogle Scholar
  20. 20.
    Spector A, John K, Fletcher JE. Binding of long-chain fatty acids to bovine serum albumin.J Lipid Res 1969;10:56–67.PubMedGoogle Scholar
  21. 21.
    Kameda K, Suzuki LK, Imai Y. Transport of fatty acid is obligatory coupled with H+ entry in spheroplasts ofEscherichia coli K12.Biochem Int 1987;14:227–234.PubMedGoogle Scholar
  22. 22.
    Kameda K. Partial purification and characterization of fatty acid binding protein(s) inEscherichia coli membranes and reconstitution of fatty acid transport system.Biochem Int 1986;13:343–350.PubMedGoogle Scholar
  23. 23.
    Knowlton AA, Apstein CA, Saouaf R, Brecher P. Heart fatty acid binding protein loss during myocardial ischemia.Circulation 1987;76(Suppl.):425.Google Scholar
  24. 24.
    Feuvray D. The role of intermediates of fatty acid metabolism in producing mitochondrial alteration in the ischemic myocardium. In Refsum H, Jynge P, Mjos OD, eds.Myocardial ischemia and protection, Churchill Livingstone 1983:45–53.Google Scholar
  25. 25.
    Pressman BC, Lardy HA. Effect of surface active agents on the latent ATPase of mitochondria.Biochim Biophys Acta 1956;21:458–466.PubMedCrossRefGoogle Scholar
  26. 26.
    Challoner DR, Steinberg D. Oxidative metabolism of myocardium as influenced by fatty acids and epinephrine.Am J Physiol 1966;211:897–902.Google Scholar
  27. 27.
    Lamers JMJ, Stinis HT, Montfoort A, Hulsmann WC. The effect of lipid intermediates on Ca2+ and Na+ permeability and (Na+ + K+)-ATPase of cardiac sarcolemma. A possible role in myocardial ischemia.Biochim Biophys Acta 1984;774:127–137.PubMedCrossRefGoogle Scholar
  28. 28.
    Messineo FC, Pinto PB, Katz AM. Palmitic acid enhances calcium sequestration by isolated sarcoplasmic reticulum.J Mol Cell Cardiol 1981;12:725–732.CrossRefGoogle Scholar
  29. 29.
    Hulsmann WC. Coronary vasodilation by fatty acids.Basic Res Cardiol 1976;71:179–191.PubMedCrossRefGoogle Scholar
  30. 30.
    Sugiyama S, Kitazawa M, Kotake K, et al. Mechanism of the antiarrhythmic action of verapamil.J Cardiovasc Pharmacol 1981;3:801–806.PubMedCrossRefGoogle Scholar
  31. 31.
    Pitts BJR, Tate CA, Van Winkle WB, et al. Parmitylcarnitine inhibition of the calcium pump in cardiac sarcoplasmic reticulum. A possible role in myocardial ischemia.Life Sci 1978;23:392–402.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Mitsuyuki Makiguchi
    • 1
  • Hideaki Kawaguchi
    • 1
  • Mamoru Tamura
    • 2
  • Hisakazu Yasuda
    • 1
  1. 1.Department of Cardiovascular MedicineHokkaido University School of MedicineSapporoJapan
  2. 2.Biophysics Division, Research Institute of Applied ElectricityHokkaido UniversitySapporoJapan

Personalised recommendations